Replies to post #379049 on Anavex Life Sciences Corp (AVXL)

[tradeherpete]

Ok but didn’t you predict there would be some that improved? Like 20 or something?

And it only makes sense to hedge the bet a little to get approval. What happens after that can be discussed over any beverage, anywhere in the World.

[boi568]

Wasn't the original endpoint just "change in cognition"? That gives no guidance whether the change is up or down. Using the new language specifies a direction and solves that minor issue. It also happens to line up with the terms that were used in reporting the Lecanemab results, allowing for an apples to apples comparison.

There has been no suggestion offered, other than by the usual trolls, that the endpoint change implies a lowering of the goalposts. I still think only a troll would try to play that card. Are you trying to play that card?

[mrplmer]

Feuerstein will add this change to his FUD publications.

[Doc328]

The original endpoint from December 2018 until September 2021 was:

1.	ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) 
 [ Time Frame: 48 weeks ] 
  
 Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo 
 2.	ADCS-ADL (Activities of Daily Living) 
 [ Time Frame: 48 weeks ] 
  
 Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo 
 

The last update, July 12, 2022 was:

1.	ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ] 
 Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) 
  
 2.	ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ] 
 Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL) 
 

Looking at a few other studies, the most common wording for AD trials endpoints is "Change from baseline". This was also the wording used for aducanumab's trials -- that led to FD approval, So the original wording was "Change from baseline", the gold approvable standard and now its "Reduction in cognitive decline assessed from baseline over 48 weeks" Of course we care about good outcomes so, on the surface, reduction from baseline sounds like its just excluding "worsening from baseline" That seems ok though it may lead to an attempt to use one-sided rather than 2-sided p values which is not the standard. The other strange part is the change in prepositional phrase from "from baseline to 48 weeks" to "from baseline over 48 weeks". Is "to" to "over" just a choice of wording or are they planning some sort of AUC type analysis which might be fine as long as the original endpoint is also released. Failing to do so will lead to another Avatar fiasco. Just my concern, I may be reading too much into the semantics.

[Steady_T]

The language change was cosmetic. It went from change in baseline to reduction in decline from baseline.

Since this will be an average over a group it is expected that some will do better than others. In the case of 2-73, based on previous data, there is likely to be some patients that improve, others that stabilize, and some that have a reduced rate of decline.

The previous language would have allowed an accelerated rate of decline to meet the "change in baseline" criteria. Not that anyone would consider that as an acceptable outcome, but it would have met the criteria based on the language. The language change made the criteria more specific.

So now the average decline rate of the group has to be slowed to meet the trial criteria. That was in reality always the case.

What may be the big surprise is the shape and center point of the distribution curve of the trial population. We could see patients in the right hand side of the curve do better than just a slowed rate of decline. That would be HUGE and unprecedented, except in the P2a trial.